Randomized, multicenter phase II trial of CAP7.1 in patients with advanced biliary tract cancers
| Autor: | Ulrich Keilholz, Stefan Kasper, Ulrich-Frank Pape, Karel Caca, Jan Kuhlmann, Nalan Utku, Arndt Vogel, Marianne Sinn |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cancer Research
medicine.medical_specialty Palliative treatment business.industry Gallbladder Medizin medicine.disease Gastroenterology Surgery Stable Disease medicine.anatomical_structure Oncology Biliary tract Internal medicine Medicine Adenocarcinoma In patient Progression-free survival business Etoposide medicine.drug |
| Popis: | 441 Background: Non-resectable biliary tract cancers (BTC) have poor prognosis, but are chemosensitive. CAP7.1 is a new chemical entity that releases etoposide in the presence of carboxylesterases, leading to higher intra-tumor etoposide (E) with improved safety and efficacy. Methods: The primary objective of this trial is to determine the rate of disease control (DCR) (stable disease, SD; partial response, PR and complete response, CR) according to Recist 1.1. of CAP7.1 in patients (pts) with BTC. Secondary objectives are progression free survival (PFS), overall survival (OS) and safety. Pts with adenocarcinoma arising from bile ducts or gallbladder were randomized (1:1) to either CAP7.1 or best supportive care (BSC) group (institutional palliative treatment). Pts in CAP7.1 arm subjected to a 3-week cyle (cy) with CAP7.1 on days 1-5 in 3-week cy was given with either 200 or 150mg/m2. until progression. At progression BSC pts were allowed to cross over to CAP7.1. Safety was assessed with CTCAE v 3.0 and efficacy after 2 cy of treatment. 18 /50 pts (9 in each study arm) finalized 1st stage and analyzed for efficacy and safety. Results: DCR in the CAP7.1 arm was 56%, with 5/9 of pts with SD (including tumor shrinkages), while all pts in the BSC arm progressed. The median PFS time was 3.5 months (95% CI, 1.9 to 8.4 months) in the CAP7.1 arm. 5 pts crossed over to the CAP7.1 arm. 2/3 pts continued CAP7.1 treatment up to 5 and 8 cycles as SD, respectively, while one pts achieved PR. The median OS time from first treatment with CAP7.1 was 5.9 months (95% CI, 2.6 to 15.3 months) over all evaluable pts, including BSC after crossing to CAP7.1. Commonly observed drug related adverse events (AE) are hematoxicity/myeolosuppression, various events of infection, alopecia, fatigue, nausea and abdominal pain, which were in general well managed. G3-4 neutropenia occurred in 4/10 pt at a dose of 150 mg/m²/d and in 6/11 pts at 200 mg/ m2/d; uncomplicated g 3-4 thrombocytopenia occurred in 2/11 pt at 200 and in 1/10 at 150 mg/ m2/d. Non-hematological AE were mainly mild or moderate e.g. abdominal pain and alopecia as most frequent AEs. Conclusions: CAP7.1 showed promising activity in therapy refractory advanced BTC patients. |
| Databáze: | OpenAIRE |
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